Lovers not Fighters

Changing a single gene eliminates gender specific sexual behavior in mice

by Dr. Barry Starr, Stanford University

How do you turn a male mouse bisexual? Or make a female mouse act like a male bisexual mouse? By knocking out a single gene called TRPC2. This gene has the instructions for making a protein that helps a mouse distinguish between males and females.

You might have predicted that a male who can't tell males from females might fall back on some sort of default behavior. And they sort of do. The males that lack the TRPC2 gene treat both male and female mice like females.

In females, you might have predicted that the female would treat all other mice as either males or females. They do no such thing. Instead, they change their behavior to become more like male mice that lack TRPC2. They act like males who think all other mice are females.

It is amazing that getting rid of a single gene had such profound effects. What is even more amazing is that getting rid of the TRPC2 gene in females essentially turned their behavior into that of bisexual males.

This result suggests that there is a sort of latent male brain in the female brain of a mouse. In other words, mice don't really have a male or a female brain. Instead, there is a default brain that becomes male or female based on how a mouse senses the world.

This is different than what a lot of people have thought. The huge differences between the ways males and females act was thought to be due to each of their brains being set up differently. A male has his brain configured one way and a female another.

This study suggests that at least in mice, this is not the case. The basic circuitry of a male and female brain is similar. It is the sensory system that is different.

The nose knows

Mice have little free will
when it comes to behavior.

Mice do not have a lot of free will when it comes to interacting with other mice. Mouse behavior in this case is almost completely determined by biology.

If you're a male, you will attack another male or try to get intimate with a female mouse. And if you're female, you'll welcome a male mouse if you are biologically ready to have a family. Or attack if you have pups.

All of this mouse behavior is channeled through the nose. How? Through special air-borne chemicals called pheromones. Males put out one kind of pheromone and females put out another.

Pheromones are detected in a special organ in the nasal cavity called the vomeronasal organ (VNO). Once there, a pheromone sets off a whole series of events that are translated into a signal to the brain. The brain then uses that signal to direct the appropriate behavior.

TRPC2 is a key player in the VNO. Mice without TRPC2 do not react to the presence of the pheromones and so can't tell the difference between males and females. As I said, this causes male and female mice to act similarly.

The fact that they act similarly suggests that the brain of a male and a female mouse are pretty similar. But there is also another possibility. It might be that TRPC2 is important for setting up a male or female brain properly.

See, because of the way the researchers did the experiment, these mice never had a TRPC2 gene. You could imagine that TRPC2 helps male and female brains develop. And maybe mice of both sexes without TRPC2 have a different brain set up than either male or female mice that have TRPC2.

This doesn't seem to be the case. When scientists remove the VNO from adult mice, the mice behave just like the mice without any TRPC2 protein. This means that TRPC2 did not affect how the brain developed. Instead the VNO and the TRPC2 protein "decide" how a mouse will react to the same and opposite sex.

This all suggests that the default of a mouse brain is to be dominant and try to make babies with whomever they can. The VNO modifies how the mouse responds depending on the sex of the mouse and the pheromones present. So there must be something male or female specific about the VNO and not necessarily the brain.

So the brain is not hardwired as a male or a female in the mouse. The brain is a certain way and the more traditional sexual behavior is determined by a properly working VNO.

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What about people?

Of course a question that naturally arises out of this research is whether something like this can explain different sexual behaviors in people. Is there a TRPC2 gene in people that causes males and females to be bisexual? Or a different gene that results in homosexuality?

The quick answer is most likely no. Human behavior is way too complex for a single gene to determine sexual behavior. But this isn't to suggest that there is nothing biological about human sexual behavior. There obviously is.

Men tend to act a certain way and females a different way. The differences between a man and a woman are not as pronounced as between a male and a female mouse, but they are there. Human sexual behavior can be thought of as a range of behaviors with most men clustered at one end and most women at the other.

And there is definitely something biological about human sexual orientation since most people are born with theirs. This is different than what a lot of people think. Many people incorrectly think that culture or how someone is raised has a significant impact on sexual orientation. These factors don't. Most research suggests that social factors like these have at best a very small effect on orientation.

We haven't yet pinned down what the biological difference is between a straight and a homosexual person. Maybe unlike mice, human brains are hardwired for a certain sexual orientation. A couple of studies that would support this have shown that the brains of gay people are different than those of straight people.

Or it could be that something similar to mice is going on. The idea would be that male and female brains are pretty similar in terms of sexual behaviors and it is just the signaling machinery that is different. Studies that support this idea have shown that gay people respond to pheromones differently than straight people.

We just don't know how a human brain works with regard to sexual behavior. We do know, though, that genes play a role. They aren't the whole story, but genes play an important part. Click here for more details.

Most likely it is the interplay of the environment and genes that results in homosexuality. By environment, I don't just mean how someone is raised (although as I said, that is sometimes a small part of it). I mean the effect the environment can have on how the brain develops very early on.

In the womb, things happen that can affect how we develop. A surge of hormones here, a viral infection there, and we are not the same as we would be without these environmental factors. Some people will have a set of genes that makes them more susceptible to such effects.

But we don't yet know what these genes are. We'll just have to wait for more research to figure out how human sexual behavior is determined. Are there male and female brains? Or is it more like in mice where the sensory machinery is male or female?

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Content provided by the Department of Genetics, Stanford University.